Surgical approach to patients with primary aldosteronism

Introduction

Primary hyperaldosteronism (PA) is characterized by an inappropriate production of aldosterone from one or both of the adrenal glands. It is one of the most common causes of endocrine-related hypertension and patients will often present with severe, medically resistant hypertension (1,2). Fortunately, approximately 40% of patients with PA will have unilateral disease, such as an aldosterone producing adenoma or unilateral adrenal hyperplasia, and thus be amenable to surgical cure (3-5). If unilateral disease is present, the patient should be considered for operative intervention (6,7). In order to determine this, the patient must undergo tumor lateralization. Noninvasive cross-sectional imaging, such as a CT or MRI scan, can be used as an initial diagnostic test; however, these tests may not identify small, subcentimeter tumors. Since many aldosteronomas are less than 1.5 cm, CT could fail to localize a tumor in up to 10–20% of patients (4-6,8,9). Furthermore, in 2010, Mathur et al. performed AVS after a CT scan on 114 patients with PA and found that CT findings can be misleading in 50% of patients. In this study, of 57 patients who had a unilateral abnormality on CT, 6 had bilateral hyperplasia and 5 had a contralateral abnormality on AVS. Thus, 11 of 57 patients with a unilateral abnormality on CT would have undergone unnecessary surgery or had the normal adrenal resected. The remaining 57 patients had either a bilateral abnormality or no abnormality on CT; however, 46 (80%) of those patients had unilateral localization on AVS. Consequently, 46 of 57 patients with bilateral abnormalities or no findings on CT would have a delay in appropriate surgical intervention, prolonging the deleterious effects of resistant hypertension (10).

Approximately 2–10% of patients who have a biochemical diagnosis of hyperaldosteronism and an adrenal mass on CT who proceed with surgical resection will have persistent hyperaldosteronism postoperatively. In these patients, the adrenal mass represents a nonfunctional cortical adenoma and the etiology of the hyperaldosteronism is either a contralateral microadenoma or bilateral adrenal hyperplasia (5,11). The incidence of non-functional cortical adenomas increases with age, from <0.2% among patients below 40 years of age, to 3–5% among patients age 40–70 and up to 7% for patients above the age of 70 (11-13).Consequently, if the CT is non-lateralizing or if the patient is older and there is a question of whether they may have a non-producing cortical adenoma, a more invasive lateralization study should be considered (4,5,11).

Arteriovenous sampling (AVS)

AVS is the most common invasive localization study for PA. AVS is performed by cannulating each adrenal vein, which is confirmed by a 5-fold increase in cortisol levels in the adrenal vein compared to the peripheral circulation (IVC), followed by measuring the aldosterone and cortisol levels from each adrenal vein. Successful lateralization occurs when there is a minimum of a four-fold increase in aldosterone to cortisol ratio from one side compared to the other (5,11). An international, multi-institutional study demonstrated that patients with unilateral PA diagnosed by AVS have a higher likelihood of achieving complete biochemical success, defined as normal suppression according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, compared to patients diagnosed by CT alone (14).

One disadvantage to AVS is the difficulty of performing the procedure. Failure rates of AVS can be as high as 80%, most commonly due to the difficulty of cannulating the right adrenal vein because of the sharp angle at which it enters the IVC (Figure 1) (4,5,11). Moreover, AVS is an invasive procedure that is not without risk, including, albeit rare, adrenal vein rupture (15). Furthermore, instrumentation of the adrenal vein can lead to a local inflammatory response and create adhesions that may make subsequent dissection more difficult. As a result, an institution may decide to proceed directly to unilateral adrenalectomy in a young patient (<35–40 years) with marked hypokalemia and a high aldosterone to renin ratio who has a large unilateral adrenal mass on CT (5,13,16).

Figure 1 Arteriovenous sampling. The right adrenal vein empties directly into the IVC whereas the left adrenal vein empties into the left renal vein, which then empties into the IVC (A). The sharp angle of the right adrenal vein to the IVC creates a technical challenge to successfully cannulate the right side (B). The left sided adrenal vein cannulation (C) is not as difficult given the more favorable angle that the left adrenal vein takes as it empties into the left renal vein. (From CollectedMed, https://collectedmed.com, with permission).

Surgical approaches

Open vs. laparoscopic

Once the tumor has been localized, surgical options include open, laparoscopic, or robotic with an anterior, lateral, or posterior approach. Since laparoscopic adrenalectomy was first described almost 30 years ago, the literature has demonstrated the safety and effectiveness of laparoscopic adrenalectomy for adrenal disease (6,17-21). Specifically, laparoscopic adrenalectomy is associated with lower morbidity, decreased hospital stay, lower rates of ileus, and decreased postoperative pain compared to open adrenalectomy (20,22-25). The preferred approach for PA is the laparoscopic technique, which includes a transabdominal or retroperitoneoscopic approach.

Laparoscopic transabdominal adrenalectomy

Transabdominal adrenalectomy can be performed via an anterior or lateral approach. With the advent of laparoscopy, the initial approach for adrenalectomy was an anterior transabdominal approach with the patient in a supine position. This provides a wide working area for the surgeon, familiar anatomic landmarks, and allows for bilateral adrenalectomy without repositioning (26). In 1992, Ganger described performing laparoscopic adrenalectomy with the patient in the lateral decubitus position. The patient is secured using a beanbag and the operating table is flexed at the waist in order to open the space between the lower rib and the iliac crest (Figure 2) (4,27). Raising a kidney rest can further expand this space. The lateral position has the advantage of gravitational autoretraction of intra-abdominal organs, which improves exposure and decreases risk of injury to surrounding structures (4,17,27).

Figure 2 Patient in the left lateral decubitus position for a laparoscopic transabdominal adrenalectomy (A) with port placement (B). (From CollectedMed, https://collectedmed.com, with permission).

However, the patient would require repositioning if bilateral adrenalectomy were necessary (28). Furthermore, while there was a decreased risk of injury to surrounding structures, the lateral transabdominal technique requires mobilization of intra-abdominal organs including the colon, liver (on the right side), or spleen/pancreas (on the left side), which risks injury and can increase operative time (Figure 3) (29).

Figure 3 Laparoscopic TA in the lateral decubitus position is favorable to the supine position because it allows for medialization of the viscera to expose the retroperitoneal (RP) space. However, TA approach still requires mobilization of the liver and colon on the right side (A) or the spleen and pancreas on the left (B), risking injury. (From CollectedMed, https://collectedmed.com, with permission). TA, transabdominal adrenalectomy.

Retroperitoneoscopic adrenalectomy

In 1995, Mercan described the endoscopic posterior retroperitoneal approach, which provides for a more direct access to the adrenal gland (9,30). The patient is in a modified prone position with two non-compressible bolsters under the chest and hips, allowing the ventral wall of the abdomen to hang freely and thus avoiding compression of the retroperitoneal space (19,27). The bed is flexed to accentuate the space between the costal margin and the iliac crest and the legs are lowered to horizontally position the back parallel to the floor (Figure 4A) (4,27).

Figure 4 Laparoscopic retroperitoneal adrenalectomy in modified prone position (A) demonstrates the location of relevant anatomy (B). Appropriate port placement is one of the most important aspects of this approach (C,D). (From CollectedMed, https://collectedmed.com, with permission).

This approach can be performed using 3 ports, which is one of the most critical steps to prepare for a successful operation (19,31). The first port should be placed 2 cm below the tip of the 12th rib (32). Care must be taken not to go too close to the 12th rib or the patient may experience postoperative neuralgia. Furthermore, the port should enter the retroperitoneum at a 45-degree angle to the 12th rib to optimize the approach to the adrenal gland with rigid laparoscopic instruments (Figure 4B,C,D) (33).

By avoiding the intra-abdominal cavity, intra-abdominal adhesions from prior operations can be avoided and mobilization of intra-abdominal organs including the liver, colon, spleen and pancreas, to provide exposure is unnecessary (Figure 5) (9,26,28,29,31-34). With this approach, the patient can undergo bilateral adrenalectomy without the need for repositioning (9,28). Furthermore, compared to the lateral transabdominal approach, the retroperitoneoscopic approach is associated with less postoperative pain, lower analgesic requirements, and a shorter hospital stay (26,30).

Figure 5 Relevant anatomy of the laparoscopic retroperitoneal approach from the right side (A) and the left side (B). (From CollectedMed, https://collectedmed.com, with permission).

However, there are several limitations to the retroperitoneoscopic approach. Although the access is more direct, the retroperitoneum is a smaller working space and the lack of familiar anatomic landmarks can be disorienting, especially for less experienced surgeons (9,28). The literature reports a learning curve of 20–25 cases required in order to complete the operation under 90 minutes (31,35). Due to the smaller working space, some prefer lateral transabdominal approach for tumors >6 cm; however, some series reported resecting tumors up to 8 cm in size with the retroperitoneoscopic approach (9,28,30,32-34). Patients with a higher BMI tend to have thick perinephric fat, which can make mobilization of the kidney more difficult (23,31,32). Although some report success in patients with higher BMI, most surgeons will prefer lateral transabdominal for a BMI >40 (34,36,37). Furthermore, studies have reported difficulty with the retroperitoneoscopic approach in patients with a large distance between the skin and Gerota’s fascia (>4 cm), which limits the ability of the instruments to dissect the adrenal gland (26,31).

Ultimately, both the lateral and posterior approaches are safe and effective. Furthermore, the majority of studies comparing the two approaches found no difference in operative time or morbidity. Thus, while there are certain factors that may make one laparoscopic approach more favorable to another, the choice of lateral transabdominal versus retroperitoneoscopic is often dependent on surgeon preference (28).

Postoperative considerations

In 2017, the Primary Aldosteronism Surgical Outcome (PASO) study published consensus guidelines for postoperative outcomes and management of patients with unilateral PA. These set of criteria consisted of clinical outcomes (blood pressure readings, use of antihypertensive medications) and biochemical outcomes (plasma concentrations of aldosterone, potassium, and renin). Patients were categorized as reaching complete, partial or absent biochemical and clinical success. The majority of patients from this study (94%) achieved complete biochemical success; however, less than half (37%) of patients achieved complete clinical success (defined as normotensive off of all antihypertensive medications) (38).

To assess the importance of a partial clinical success after unilateral adrenalectomy, another international multi-institutional study was performed. In the International CONNsortium study, researchers examined the outcomes for patients who remained hypertensive requiring antihypertensive medication postoperatively. Results demonstrated biochemical and clinical cure in 27% of patients, clear improvement in 31% and no clear improvement in 41.8%. However, of the patients with no clear success, the mean systolic and diastolic blood pressure decreased by 9 and 3 mmHg, respectively. Consequently, even those who are unable to wean off of their antihypertensives, there is still a potential benefit with surgery (1). In general, antihypertensive medications should be decreased in dose or stopped entirely postoperatively with close follow-up after discharge (4).

Due to the high rate of biochemical cure postoperatively, all potassium supplements and potassium-sparing diuretics should be stopped immediately to prevent hyperkalemia (4,8,27). Electrolytes should be checked on postop day 1 and then weekly for the subsequent 4 weeks (4,27).

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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